Acute taVNS lowered sequence baroreflex sensitivity in healthy men
A brief session of transcutaneous auricular vagus nerve stimulation did not produce the clean autonomic boost many clinicians might expect. In this exploratory, non-randomised study of 18 healthy men, acute left-cymba stimulation was associated with a lower spontaneous sequence baroreflex sensitivity during the stimulation phase than during the pre-stimulation phase, while Mayer-band coherence and representative heart rate variability indices did not show a detectable shift.
The direction of the effect matters. Rather than reflecting a simple increase in cardiac vagal output, the findings point to a more complicated interaction between auricular afferent input, central autonomic integration, and the physiological state in which the stimulation is delivered.
Sequence baroreflex sensitivity moved in the opposite direction from the expected vagal narrative
Participants completed fixed-order five-minute pre, stimulation, and post phases, with no sham condition. The primary physiological signal of interest, centrally designated post hoc, was spontaneous sequence BRS. During stimulation, BRSseq fell from 8.54 ± 5.57 to 6.49 ± 3.89 ms/mmHg, with a paired mean difference of −2.05 and a BCa 95% confidence interval from −3.81 to −1.10. The Wilcoxon p value was 2.29 × 10−5, and Cohen’s d_z was −0.74.
The signal was not confined to a few outliers. Negative within-person differences appeared in 17 of the 18 participants, which gives the result a consistency that is hard to ignore even in a small exploratory cohort. In physiological terms, reduced sequence BRS suggests a weaker beat-to-beat coupling between systolic blood pressure ramps and subsequent R-R interval adjustments during the stimulation window.
Systolic blood pressure was higher during stimulation. That observation fits an acute autonomic shift rather than a neutral session effect, although the design cannot separate stimulation-specific physiology from context, expectancy, or other uncontrolled influences.
Why Mayer-wave coherence stayed unchanged while baroreflex gain fell
The dissociation between BRSseq and Mayer-band coherence is clinically and mechanistically important. Mayer-band coherence captures the consistency of the linear frequency-domain relationship between systolic blood pressure and R-R interval oscillations near 0.1 Hz, but it does not measure the amplitude of baroreflex gain in ms/mmHg. In contrast, sequence BRS estimates the slope of the blood pressure–R-R interval relationship and is a more direct readout of spontaneous cardiac baroreflex responsiveness.
A fall in sequence BRS can therefore occur without a parallel change in coherence. The two measures are not interchangeable, and the present data reinforce that point in a setting where investigators and readers may otherwise be tempted to treat “autonomic change” as a single construct. In practical physiological terms, the stimulation may have altered how strongly the heart responded to pressure changes without shifting the regularity of the low-frequency oscillatory coupling that defines Mayer-band coherence.
No detectable differences emerged for the representative heart rate variability indices. That result argues against assuming that any auricular vagus intervention will leave a visible footprint across every common autonomic marker in the same session.
An exploratory design with clear limits on causal interpretation
The study was explicitly exploratory, non-randomised, open-label, and fixed in order. Those features make the results useful as a physiological signal-detection exercise, but they also leave major interpretive gaps. Without sham stimulation, the session cannot establish stimulation-specific engagement. Without randomisation or counterbalancing, order effects remain plausible. Without blinding, expectancy and nonspecific sensory effects cannot be excluded.
The cohort was also narrow: 18 healthy men. No adverse events were reported after the sessions, which is reassuring from a short-term safety standpoint, but the sample is too small and too selective to inform broader clinical tolerability, sex-specific responses, or any patient-level therapeutic threshold.
Recovery of BRS was not established. In a bedside context, that matters because a transient autonomic perturbation only becomes clinically meaningful if its time course, reproducibility, and relationship to symptoms or hemodynamic risk are known. None of those questions were answered here.
What this means for taVNS as a monitoring target
The most useful implication from this study is not that auricular stimulation reliably suppresses baroreflex function, but that sequence BRS may be a more sensitive session-level physiological response measure than HRV or Mayer-wave coherence for some taVNS paradigms. The authors’ data support prospective evaluation of sequence BRS for future work, especially because it measures blood pressure–R-R interval gain directly rather than relying on a proxy of oscillatory coupling.
Still, the current findings do not establish clinical utility. They do not show a treatment effect on disease, do not define a monitoring threshold, and do not prove a direct vagal inhibitory mechanism. The physiological response could reflect central autonomic processing, local sensory input, baseline autonomic state, or a combination of all three.
A sham-controlled replication is now the essential next step. Until then, this study stands as a caution against assuming that auricular vagus stimulation uniformly enhances parasympathetic cardiovascular tone; in these healthy volunteers, the immediate measurable effect moved in the opposite direction for sequence baroreflex gain, while other familiar autonomic markers remained unchanged.